MACROPHAGES ISOLATED FROM HUMAN ATHEROSCLEROTIC PLAQUES PRODUCE IL-8,AND OXYSTEROLS MAY HAVE A REGULATORY FUNCTION FOR IL-8 PRODUCTION

Oxysterols are biologically active molecules generated during oxidatio n of LDL. Several of these oxysterols were found in macrophage-denived foam cells from human atherosclerotic tissue (eg, 7-hydroxycholestero l, 7-ketocholesterol, 5-epoxycholesterol, and 25-hydroxycholesterol). A specific stimulation of interleukin-8 (IL-8) production by oxidized LDL (oxLDL) has been shown by other investigators. In foam cells from human atherosclerotic tissue, we found high levels of IL-8 (183.1 pg/1 0(6) cells) compared with monocytes (23.2 pg/10(6) cells) or monocyte- derived macrophages in culture (1.5 pg/10(6) cells). When monocytes an d monocyte-derived macrophages, in vitro, were exposed to a series of different oxysterols, we found that all oxysterols tested had a tenden cy to stimulate IL-8 production but that 25-hydroxycholesterol was the most potent one. This stimulation of IL-8 production was time and dos e dependent and could be blocked by cycloheximide. These results indic ate that oxysterols in oxLDL may have a regulatory effect on IL-8 prod uction. IL-8, a potent chemoattractant, may play a role in the recruit ment of T lymphocytes and smooth muscle cells into the subendothelial space and may contribute to the formation of atherosclerotic lesions.